Institute of Systems Biology and Bioinformatics, National Central University, Jhong-Li, Taiwan.
Biotechnol J. 2012 Nov;7(11):1367-75. doi: 10.1002/biot.201200003. Epub 2012 Jul 10.
Aptamers are rare functional nucleic acids with binding affinity to and specificity for target ligands. Recent experiments have lead to the proposal of an induced-fit binding mechanism for L-argininamide (Arm) and its binding aptamer. However, at the molecular level, this mechanism between the aptamer and its coupled ligand is still poorly understood. The present study used explicit solvent molecular dynamics (MD) simulations to examine the critical bases involved in aptamer-Arm binding and the induced-fit binding process at atomic resolution. The simulation results revealed that the Watson-Crick pair (G10-C16), C9, A12, and C17 bases play important roles in aptamer-Arm binding, and that binding of Arm results in an aptamer conformation optimized through a general induced-fit process. In an aqueous solution, the mechanism has the following characteristic stages: (a) adsorption stage, the Arm anchors to the binding site of aptamer with strong electrostatic interaction; (b) binding stage, the Arm fits into the binding site of aptamer by hydrogen-bond formation; and (c) complex stabilization stage, the hydrogen bonding and electrostatic interactions cooperatively stabilize the complex structure. This study provides dynamics information on the aptamer-ligand induced-fit binding mechanism. The critical bases in aptamer-ligand binding may provide a guideline in aptamer design for molecular recognition engineering.
适体是一种具有结合亲和力和对靶配体特异性的稀有功能核酸。最近的实验提出了 L-精氨酸酰胺（Arm）及其结合适体的诱导契合结合机制。然而，在分子水平上，适体与其偶联配体之间的这种机制仍知之甚少。本研究采用显式溶剂分子动力学（MD）模拟，在原子分辨率水平上研究了适体与 Arm 结合的关键碱基以及诱导契合结合过程。模拟结果表明，Watson-Crick 碱基对（G10-C16）、C9、A12 和 C17 碱基在适体与 Arm 的结合中起重要作用，并且 Arm 的结合导致适体构象通过一般的诱导契合过程进行优化。在水溶液中，该机制具有以下特征阶段：（a）吸附阶段，Arm 与适体的结合位点通过强静电相互作用锚定；（b）结合阶段，Arm 通过氢键形成适配体的结合位点；（c）复合物稳定阶段，氢键和静电相互作用协同稳定复合物结构。本研究为适体-配体诱导契合结合机制提供了动力学信息。适体-配体结合的关键碱基可能为分子识别工程中的适体设计提供指导。
